19-54207569-G-C

Variant names:

• chr19-54207569-G-C
• rs754474712
• NM_001013.4:c.579G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_001013.4(RPS9):​c.579G>C​(p.Glu193Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,456,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: RPS9 NM_001013.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72
• Publications: 0 publications found

Genes affected

RPS9 (HGNC:10442): (ribosomal protein S9) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S4P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

ENSG00000300077 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2397395).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS9	NM_001013.4	MANE Select	c.579G>C	p.Glu193Asp	missense	Exon 5 of 5	NP_001004.2
	RPS9	NM_001321701.2		c.579G>C	p.Glu193Asp	missense	Exon 5 of 5	NP_001308630.1	P46781
	RPS9	NM_001321702.2		c.579G>C	p.Glu193Asp	missense	Exon 5 of 5	NP_001308631.1	P46781

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS9	ENST00000302907.9	TSL:1 MANE Select	c.579G>C	p.Glu193Asp	missense	Exon 5 of 5	ENSP00000302896.4	P46781
	RPS9	ENST00000391753.6	TSL:1	c.579G>C	p.Glu193Asp	missense	Exon 4 of 4	ENSP00000375633.2	P46781
	RPS9	ENST00000441429.1	TSL:1	c.*1043G>C		3_prime_UTR	Exon 3 of 3	ENSP00000414314.1	C9JM19

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1456318 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724170

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 85782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4178

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1109920

Other (OTH) AF: 0.0000166 AC: 1 AN: 60066

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.048	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.48	N
PhyloP100		1.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.18
Sift	Benign	0.055	T
Sift4G	Uncertain	0.059	T
Polyphen		0.88	P
Vest4		0.43
MutPred		0.17		Loss of helix (P = 0.2662)
MVP		0.42
MPC		1.3
ClinPred		0.51	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.0
Varity_R		0.17
gMVP		0.42
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs754474712; hg19: chr19-54711437;